The Origin of Specific Protein- 113 



arisen during the course of embryonic development, and direct anal- 

 ysis shows this to he so. The adult pattern is the end product of a 

 long secpience of gradual changes during ontogeny. 



The existence of isozymes poses important problems for the origin 

 of specific proteins. Each isozyme may he the responsibility of one 

 or two genes, or the several isozymes may represent modifications of a 

 single gene product. The latter case would represent molecular differ- 

 entiation. A fully satisfactory explanation for the origin of isozymes 

 can scarcely be made until isozymic differences are related to molec- 

 ular structure. At least five kinds of molecular changes may be 

 invoked to produce different though closely related isozymes: Small 

 changes in amino acid sequence, amidation of earhoxyl groups, con- 

 jugation with small molecules, polymerization of different suhunits, 

 and changes in conformation achieved by folding the same primary 

 structure in different ways. All these possibilities have served to ex- 

 plain, with varying degrees of experimental support, the existence of 

 numerous enzymes in isozymic forms. Polygenic control will clearly 

 be indicated wherever isozymes are found to differ in primary struc- 

 ture. Other distinctions are more plausibly attributed to modifications 

 imposed secondarily upon a single basic gene product. 



The esterase enzymes have been extensively investigated with refer- 

 ence to both ontogenetic (Markert and Hunter, 1959) and genetic 

 control (Wright, 1961). The esterases compose a large family of 

 closely related but distinguishable enzymes. Each tissue of most 

 animals that have been examined contains a characteristic repertory 

 of these esterases in distinctive patterns of concentration. The patterns 

 arise gradually during embryonic development. However, these differ- 

 ent esterases are not all isozymes of one another. Wright (1961) has 

 shown in an investigation of Drosophila enzymes that an esterase 

 (Fig. 10) is present in position 4 in one strain and in position 5 in 

 another strain. Hybrids between these strains have esterases in both 

 positions. The genetic evidence strongly suggests that each of these 

 esterases is controlled by an allele of a single gene; the heterozygote 

 would then possess both esterases, as is apparent in the offspring from 

 a cross between the two strains (Fig. 10) . 



In Wright's investigation no isozymes of esterase have yet been 

 identified, although the genetic control of specific protein structure 

 is clearly demonstrated. However, Allen (1960) has shown in Totra- 

 hymena that the final structure of the molecule can also he the re- 

 sponsibility of cytoplasmic mechanisms emerging during the course 

 of cellular differentiation. Allen's investigation demonstrated that 

 allelic genes control alternate groups of four esterases in Tetrahymena. 



